Therapeutic restoration of miR-96 prevents hearing loss in mice through modulation of noise-induced and genetic pathways.

Hearing loss often arises from impairments in multiple genes, complicating therapeutic development. MicroRNAs, as master regulators, offer promising targets for complex diseases. We explored 's roles in hair cell (HC) function and noise-induced hearing loss (NIHL), finding that , not , mice exhibited progressive hearing loss due to gene regulatory network dysregulation from loss in HCs not spiral ganglion neurons (SGNs). Viral-mediated delivery of into the inner ear partially rescued hearing of mice. Tamoxifen-induced depletion of in adult ; mice led to hearing loss, with , , , and upregulation and , , , and downregulation. Furthermore, noise trauma reduced , altering , , , , , , and expression, whereas overexpression protected hearing against noise by reversing the expression of , , and . Our findings underscore 's essential role in adult hearing maintenance and NIHL prevention, presenting it as a promising therapeutic target.